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Originally published In Press as doi:10.1074/jbc.M707765200 on October 25, 2007

J. Biol. Chem., Vol. 283, Issue 2, 1076-1083, January 11, 2008
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Two Modes of Degradation of the Tramtrack Transcription Factors by Siah Homologues*

Sarah E. Cooper1, Christopher M. Murawsky, Nicholas Lowe, and Andrew A. Travers

From the Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, United Kingdom

The Siah proteins, mammalian homologues of the Drosophila Sina protein, function as ubiquitin-protein isopeptide ligase enzymes to target a wide range of cellular proteins for degradation. We report here a novel Drosophila protein that is homologous to Sina, named Sina-Homologue (SinaH). We show that it can direct the degradation of the transcriptional repressor Tramtrack (Ttk) using two different mechanisms. One is similar to Sina and requires the adaptor Phyllopod, and the other is a novel mechanism of recognition. This novel mode of targeting for degradation is specific for the 69-kDa Ttk isoform, Ttk69. Ttk69 contains a region that is required for binding of SinaH and for SinaH-directed degradation. This region contains an AXVXP motif, which is the consensus sequence found in Siah substrate proteins. These results suggest that degradation directed by SinaH differs from that directed by Sina and is more similar to that found in vertebrates. We speculate that SinaH may be involved in regulating the levels of developmentally important transcription factors.


Received for publication, September 17, 2007 , and in revised form, October 23, 2007.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported by a Medical Research Council studentship. To whom correspondence should be addressed. Tel.: 44-1223-402233; Fax: 44-1223-412142; E-mail: scooper{at}mrc-lmb.cam.ac.uk.


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